Enhanced extracellular vesicle production and ethanol-mediated vascularization bioactivity via a 3D-printed scaffold-perfusion bioreactor system

Patel, Divya B.; Luthers, Christopher R.; Lerman, Max J.; Fisher, John P.; Jay, Steven M.

doi:10.1016/j.actbio.2018.11.024

Cited by 102 publications

(119 citation statements)

References 36 publications

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“…Exosomes derived from MSCs are known to have intrinsic tissue regenerative effects; that is, they induce angiogenesis and cellular proliferation and inhibit fibrosis [2]. However, their widespread therapeutic use as drug carriers is currently hampered by their limited cellular secretion [18].…”

Section: Discussionmentioning

confidence: 99%

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Boosting the biogenesis and secretion of mesenchymal stem cell-derived exosomes

Wang

Bonacquisti

Nguyen

2020

Preprint

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A limitation to using exosomes to their fullest potential is their limited secretion from cells, a major bottleneck to efficient exosome production and application. This is especially true for mesenchymal stem cell (MSCs), which can self-renew but have limited expansion capacity, undergoing senescence after only a few passages, with exosomes derived from senescent stem cells showing impaired regenerative capacity compared to young cells. Here we examined the effects of small molecule modulators capable of enhancing exosome secretion from MSCs. Treatment of MSCs with a combination of methyldopamine and norepinephrine robustly increased exosome production by three-fold without altering the ability of the MSC exosomes to induce angiogenesis, polarize macrophages to the anti-inflammatory phenotype, or inhibit fibrosis. These small molecule modulators provide a promising means to increase exosome production by MSCs.

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Section: Discussionmentioning

confidence: 99%

“…To date, upscaling of exosome production has involved increasing the volume of cell culture from flasks to containers, bioreactors, or hollow fibers [18,19]. These methods require substantial volumes and are impractical for large-scale production.…”

Section: Discussionmentioning

confidence: 99%

Boosting the biogenesis and secretion of mesenchymal stem cell-derived exosomes

Wang

Bonacquisti

Nguyen

2020

Preprint

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“…Some studies have reported that exosome produced by 3D cultures (Exos/EVs-3D) has more advantages than exosome produced by 2D cultures (Exos/EVs-2D) [50][51][52][53][54][55][56][57] in terms of the size, content, function and production efficiency of exosomes. The functions of exosomes differ according to their content, while Exos/EVs-3D contain a different profile of proteins and genetic materials compared to Exos/EVs-2D [52] .…”

Section: Culture For Exosome Generationmentioning

confidence: 99%

“…Improving the productivity and functions of exosomes [57]; Designing scaffolds with more optimized geometric structure; Bone defect repair [72]; Osteoangiogenesis [73]; Cartilage repair [74];…”

Section: Culture For Exosome Generationmentioning

confidence: 99%

“…3D printing has been well used in cartilage tissue repair, and to adopt the great bioeffects of exosome into 3D printing technology, there are two break points for further development. One is to improve the productivity and functions of exosomes by using optimized 3D culture microenvironment, which can be precisely designed and printed with 3D bio-printers [57] . The other is to design advanced bio-mimic scaffolds with more optimized geometric structure and better incorporate with exosomes, thus enhancing the therapeutic effects of exosomes or EVs [72][73] .…”

Section: Bio-printingmentioning

confidence: 99%

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Exosomes in osteoarthritis and cartilage injury: advanced development and potential therapeutic strategies

et al. 2020

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Articular cartilage injury is a common clinical problem, which can lead to joint dysfunction, significant pain, and secondary osteoarthritis (OA) in which major surgical procedures are mandatory for treatment. Exosomes, as endosome-derived membrane-bound vesicles, participating in intercellular communications in both physiological and pathophysiological conditions, have been attached great importance in many fields. Recently, the significance of exosomes in the development of OA has been gradually concerned, while the therapeutic value of exosomes in cartilage repair and OA treatment has also been gradually revealed. The functional difference of different types and derivations of exosomes are determined by their specific contents. Herein, we provide comprehensive understanding on exosome and OA, including how exosomes participating in OA, the therapeutic value of exosomes for cartilage injury/OA, and related bioengineering strategies for future therapeutic design.

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HOTAIR‐Loaded Mesenchymal Stem/Stromal Cell Extracellular Vesicles Enhance Angiogenesis and Wound Healing

Born

Chang

Shoureshi

et al. 2021

Adv Healthcare Materials

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Chronic wounds remain a substantial source of morbidity worldwide. An emergent approach that may be well-suited to induce the complex, multicellular processes such as angiogenesis that are required for wound repair is the use of extracellular vesicles (EVs). EVs contain a wide variety of proteins and nucleic acids that enable multifactorial signaling. Here, the capability of EVs is leveraged to be engineered via producer cell modification to investigate the therapeutic potential of EVs from mesenchymal stem/stromal cells (MSCs) transfected to overexpress long non-coding RNA HOX transcript antisense RNA (HOTAIR). HOTAIR is previously shown by the authors' group to be critical in mediating angiogenic effects of endothelial cell EVs, and MSCs are chosen as EV producer cells for this study due to their widely reported intrinsic angiogenic properties. The results indicate that MSCs overexpressing HOTAIR (HOTAIR-MSCs) produce EVs with increased HOTAIR content that promote angiogenesis and wound healing in diabetic (db/db) mice. Further, endothelial cells exposed to HOTAIR-MSC EVs exhibit increased HOTAIR content correlated with upregulation of the angiogenic protein vascular endothelial growth factor. Thus, this study supports EV-mediated HOTAIR delivery as a strategy for further exploration toward healing of chronic wounds.

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Enhanced extracellular vesicle production and ethanol-mediated vascularization bioactivity via a 3D-printed scaffold-perfusion bioreactor system

Cited by 102 publications

References 36 publications

Boosting the biogenesis and secretion of mesenchymal stem cell-derived exosomes

Boosting the biogenesis and secretion of mesenchymal stem cell-derived exosomes

Exosomes in osteoarthritis and cartilage injury: advanced development and potential therapeutic strategies

HOTAIR‐Loaded Mesenchymal Stem/Stromal Cell Extracellular Vesicles Enhance Angiogenesis and Wound Healing

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